Opioid-induced hyperalgesia: is it clinically relevant for the treatment of pain patients?

Pain Manag Nurs. 2013 Sep;14(3):e67-83. doi: 10.1016/j.pmn.2011.04.002. Epub 2011 Jun 25.


There is a curious and paradoxic phenomenon, reliably demonstrated in animal models, that consists of an increased sensitivity to pain that is apparently induced by the very opioid drugs used to ameliorate the pain. This phenomenon is termed "opioid-induced hyperalgesia." Whether opioid-induced hyperalgesia occurs in humans, and, if so, to what extent and consequence, is far less established. This is a critical question for attempting to treat pain. If opioid-induced hyperalgesia develops in a patient, it would masquerade as tolerance (because the clinical effectiveness of the opioid would be diminished), yet the appropriate clinical adjustment would be precisely the opposite to that of tolerance. It would be to decrease, rather than increase, the dose of opioid. We review the evidence, particularly the clinical evidence, about opioid-induced hyperalgesia and the postulated mechanisms. We conclude that given the clinical ramifications, opioid-induced hyperalgesia is one of the most understudied important aspects of opioid research.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Animals
  • Drug Tolerance*
  • Humans
  • Hyperalgesia / chemically induced*
  • Pain / drug therapy*
  • Pain Measurement


  • Analgesics, Opioid